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Dieser Ubersichtsartikel beschreibt alle relevanten Aspekte entsprechend der neuen S2k-Leitlinie der Deutschen Gesellschaft fur Urologie (DGU) zur Diagnostik und Behandlung der IC/BPS (interstitielle Zystitis/Blasenschmerzsyndrom). Eine Aufstellung notwendiger und optionaler Untersuchungen und der Notwendigkeit einer Ausschlussdiagnostik werden zusammenfassend dargestellt und gewertet. Auch entsprechend aufgelistete Therapieoptionen (von konservativen, oral-medikamentosen, komplementar-medizinischen bis hin zu intravesikalen und interventionell-operativen Verfahren) geben dem Leser einen guten Uberblick uber die Inhalte der Leitlinie und moglicher therapeutischer Ansatze. Letztlich werden auch Ubersichten der Empfehlungen inklusive Konsens der Leitliniengruppe in verschiedenen Infoboxen beschrieben.

Der terminalen Niereninsuffizienz liegen ganz verschiedene Erkrankungen zugrunde, entsprechend unterscheiden sich die Dialysepatienten, die auf eine Transplantation hoffen, in weiten Bereichen. Per Gesetz ist vorgeschrieben, dass bei jedem Dialysepatienten die Eignung fur eine Nierentransplantation gepruft werden muss. Aufgrund der grosen burokratischen Anforderungen des Gesetzgebers an diesen Prozess und der individuellen sehr hohen Krankheitsschwere von Dialysepatienten ist die Uberprufung der Eignung nicht leicht zu standardisieren, sehr zeitaufwandig und komplex. Zusatzlich hat ein Dialysepatient ein sehr hohes Risiko, Folgekrankheiten zu entwickeln, die eine Eignung zur Transplantation gefahrden. Damit kommt der konstanten und konsequenten Uberprufung der Eignung der Patienten auch nach der Aufnahme auf die Warteliste (Wartelistenfuhrung) eine grose Bedeutung zu. Der Schlussel fur den Sprung auf die Warteliste und damit die erfolgreiche Transplantation ist eine enge und vertrauensvolle Kooperation zwischen dem Dialyse- und Transplantationszentrum. Leider fuhrt die in Deutschland auserordentlich lange Wartezeit fur ein Organ deswegen nicht nur zu einer Gefahrdung des Transplantationserfolgs, sie erhoht gleichzeitig auch den Aufwand der Transplantationszentren durch eine verlangerte Wartelistenfuhrung betrachtlich.

In this review article, the authors describe all relevant aspects of the new S2k guideline from the German Society of Urology (Deutschen Gesellschaft für Urologie, DGU) for the diagnosis and treatment of IC/PBS (interstitial cystitis/painful bladder syndrome). A list of necessary and optional examinations and the necessity of diagnosis of exclusion are summarized and evaluated. The treatment options listed (ranging from conservative, oral drug, and complementary medicine to interventional surgical procedures) also give the reader a good overview of the contents of the guideline and possible therapeutic approaches. Finally, the recommendations including consensus of the guideline group are also summarized in various information boxes.

The number of organ donations in Germany decreased by 32.3% between 2010 and 2017. For this reason, more than 1500 fewer organ transplantations were performed in 2017 than in 2010.What are the causes of this development?Analysis of available statistics and scientific publications.A decline of the organ donation potential can be ruled out as the cause of the declining organ donation figures, since the number of patients who were eligible for organ donation from a medical point of view increased during the period under consideration. Similarly, there is no indication that a change in the population's attitude towards organ donation can be held responsible for this development. The decline is rather due to a recognition and reporting deficit of potential organ donors. The extent of this deficit differs considerably between different hospitals and is not only responsible for the decline in the donor rate in recent years, but also for the low donor numbers in Germany by international standards.The low organ donation figures in Germany are due to a recognition and reporting deficit. The number of organ donations could be considerably increased by improving the internal processes in hospitals.

Das Risiko fur eine Tumorentwicklung nach Transplantation ist im Vergleich zur Normalbevolkerung erhoht, und die Prognose von Patienten mit Tumor nach Transplantation ist meist eingeschrankt. Deswegen sollte die Entwicklung eines Tumors nach Transplantation verhindert werden. Daraus ergeben sich wichtige Implikationen fur das Management bei Transplantation hinsichtlich einer moglichen Tumorentwicklung. Tumoren nach Transplantation konnen aus einer vorherigen Tumorerkrankung rekurrieren, durch den Spender ubertragen werden oder neu entstehen. Letztlich ist bei Durchfuhrung der Transplantation immer das Risiko einer Tumorentwicklung mit dem Nutzen der Transplantation abzuwagen und sollte individuell fur die einzelne Spender-Empfanger-Konstellation erfolgen. Der Patient sollte uber das Risiko einer Tumorentwicklung (Rekurrenz, Transmission oder Neuentstehung) bei der Listung zur Transplantation aufgeklart werden. Dieser Ubersichtsartikel fasst die Daten zur jeweiligen Inzidenz der Tumorentwicklung nach Transplantation zusammen und liefert somit Anhaltspunkte fur die Aufklarung und das Management von Patienten hinsichtlich der Tumorentwicklung nach Transplantation.

Erratum zu: Urologe 2019 https://doi.org/10.1007/s00120-019-01054-2 Leider ist in der Infobox 5 ein Fehler aufgetreten. Korrekt muss es hier „Komplementarmedizinische Therapie – Empfehlungen und Konsens“ heisen.

Die Immunsuppression, welche die Abstosung der transplantierten Nieren verhindert, geht mit einem erhohten Risiko fur die Tumorentwicklung einher. Andere Langzeitkomplikationen nach Transplantation, wie die des kardiovaskularen Systems oder Infektionen, nehmen an Bedeutung ab, sodass Tumoren sich zur fuhrenden Ursache der hohen Mortalitat in dieser Bevolkerungsgruppe entwickeln werden. Eine Reihe von Faktoren ist neben der Menge an Immunsuppression fur die Tumorentwicklung von Bedeutung, so u. a. die die genetische Disposition, Viren und maligne Vorerkrankungen. Die Reduktion der Immunsuppression sowie eine konsequente und dem spezifischen Risiko angepasste Tumorvorsorge sind gegenwartig die wichtigsten Masnahmen zur Reduktion des Risikos, solange neue Formen der Immunsuppression bzw. die Induktion immunologischer Toleranz gegenuber dem Transplantat noch nicht zur Verfugung stehen.

Die Option der Nierentransplantation muss bei allen Patienten mit einer terminalen Niereninsuffizienz gepruft werden, da die Nierentransplantation im Vergleich mit allen Dialyseverfahren dem Patienten nicht nur mehr Lebensqualitat bietet, sondern auch das Patientenuberleben signifikant verlangert. Fur den Patienten ist die Transplantation durch eine Lebendnierenspende optimal, da hierdurch die Wartezeit minimiert wird und Transplantatfunktionsdauer und Lebenserwartung am besten sind. Fur den Spender verbleibt jedoch ein vornehmlich operationsbedingtes Restrisiko. Nach der Transplantation bedarf es einer sehr sorgfaltigen Betreuung besonders in den ersten 6 Monaten, in denen das Rejektions- und das Infektionsrisiko am hochsten sind. Langerfristig bedarf es einer sorgsamen Tumorvorsorge und einer konsequenten Behandlung der kardiovaskularen Risikofaktoren. Voraussetzung fur eine optimale Betreuung dieser Patienten ist eine enge Zusammenarbeit zwischen einem Transplantationszentrum und niedergelassenen Arzten.

Mit den Calcineurininhibitoren Ciclosporin A und Tacrolimus, den DNA-Synthesehemmern Mycophenolsaure und Azathioprin und nicht zuletzt den TOR-Inhibitoren Everolimus und Sirolimus stehen derzeit eine Vielzahl von Medikamenten fur die Immunsuppression nach Nierentransplantation zu Verfugung. Diese werden noch durch Antikorper und Steroide erganzt. In dem vorliegenden Artikel werden neben den grundlegenden Daten zur Pharmakokinetik, dem Nebenwirkungsprofil und dem Interaktionspotenzial der Immunsuppressiva die Moglichkeiten und Grenzen verschiedener derzeit eingesetzter Medikamentenkombinationen einschlieslich aktueller Richtlinien der Rejektionstherapie diskutiert.

FTY720 is a novel immunomodulator being investigated for rejection prophylaxis in renal transplantation when combined with full-dose cyclosporine (CsA; FDC). This 1-year phase II study compared FTY720 plus FDC (Neoral) with FTY720 plus reduced-dose CsA (RDC) and mycophenolate mofetil (MMF) plus FDC in de novo renal transplant patients. Patients were randomized 2:2:2:1 to FTY720 5 mg plus RDC (n = 72); FTY720 2.5 mg plus RDC (n = 74); FTY720 2.5 mg plus FDC (n = 76); or MMF plus FDC (n = 39) for 12 months. CsA exposure in the RDC group was reduced on average by 50% as assessed by C(2) monitoring. The primary efficacy endpoint was the composite incidence of biopsy-proven acute rejection (BPAR), graft loss, death or premature study discontinuation. The incidences for this composite endpoint were 24% and 22%, respectively, for FTY720 5 mg plus RDC and FTY720 2.5 mg plus FDC versus 39% for MMF plus FDC. Patients receiving FTY720 2.5 mg plus RDC were discontinued from treatment due to risk of under-immunosuppression. FTY720 2.5 mg plus FDC and FTY720 5 mg plus RDC were safe and effective in de novo renal transplant patients over 12 months.

BACKGROUND Radiocontrast medium- (RM) associated nephrotoxicity continues to be a common cause of acute renal failure and may lead in patients with pre-existing chronic renal insufficiency even to end-stage renal failure requiring chronic dialysis. Since extracorporeal removal of RM after RM administration has been shown to be effective but does not prevent radiocontrast-induced nephropathy, the effect of a simultaneous dialysis during RM administration on renal function is not clear. METHODS In a prospective, randomized and controlled trial, we studied the effect of a 4-hour online dialysis during RM (iomeprol) application in patients with advanced chronic renal failure (serum creatinine > or = 3 mg/dl) undergoing coronary angiography. All patients received hydration with saline before and after standardized coronary angiography and were randomized to receive a simultaneous high-flux hemodialysis (7 patients, HD group) or to control group (10 patients). 24-hour creatinine clearance (CrCl) was measured in all patients before, 1 week and 8 weeks after coronary angiography. The clinical follow-up comprised 8 weeks after RM application. RM plasma levels were measured in both groups 15, 30, 60 minutes, 2, 4, 12, 24, 48 and 72 hours after application by high-pressure liquid chromatography. RESULTS At baseline, CrCl (19 +/- 10 vs 17 +/- 7 ml/min), percentage of diabetics (57 vs 70%) and dose of RM (77 +/- 27 vs 86 +/- 21 ml) were similar in both groups. Pharmacokinetics: Total clearance of iomeprol was significantly higher (54 +/- 15 vs 20 +/- 12 ml/min, p < 0.001) and the area under curve (AUC) was significantly lower (23 +/- 10 g x h/l vs 94 +/- 57 g x h/l, p < 0.001) in the HD group compared to control group. RM peak plasma levels 15 min after application were not different in both groups (3.0 +/- 1.1 vs 4.2 +/- 1.7 mmol/l, NS), however, significantly lower 60 min (1.6 +/- 0.4 vs 3.7 +/- 1.5 mmol/l, p < 0.01) and 240 min (0.7 +/- 0.3 vs 2.3 +/- 0.7 p < 0.001) after angiography. CLINICAL RESULTS CrCl showed no difference 1 week (24 +/- 11 vs 19 +/- 9 ml/min, ns) and 8 weeks (24 +/- 5 vs 20 +/- 9 ml/min, NS) after angiography from baseline or between the groups. In each group, 2 patients developed end-stage renal disease and requested permanent dialysis during the 8-week follow-up. CONCLUSION Simultaneous dialysis reduces AUC of iomeprol significantly, however, does not influence plasma peak concentration after angiography. Renal function and incidence of end-stage renal failure were not influenced by online-dialysis.

Background andobjectivesThecalcimimeticcinacalcet reduced therisk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients. Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified. ResultsOlderpatients hadhigher baselineprevalenceof diabetesmellitusandCV comorbidity. Annualizedrates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. Conclusions In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone. Clin J Am Soc Nephrol 10: ccc–ccc, 2015. doi: 10.2215/CJN.07730814

Ein Phaochromozytom ist eine seltene Differenzialdiagnose einer hypertensiven Krise. Dargestellt wird der Verlauf eines Patienten, der aufgenommen wurde nach rezidivierenden Episoden von Ubelkeit, Erbrechen, Hautblasse und paroxysmalen Blutdruckspitzen, zuletzt mit Orthopnoe bei Lungenodem und Thoraxschmerzen. Phaochromozytome gehen von den chromaffinen Zellen des Nebennierenmarks aus und sind fur etwa 0,2% der arteriellen Hypertonieerkrankungen ursachlich; 85% sind im Nebennierenmark lokalisiert, doch sie kommen auch im thorakalen und abdominalen Grenzstrang vor. Typische Symptome sind paroxysmaler oder anhaltender Bluthochdruck, Kopfschmerzen, Schwitzen, Tachykardie und Hautblasse. Initial gehoren zur Diagnostik u. a. eine 24-Stunden-Sammelurinuntersuchung, Katecholaminbestimmungen im Plasma und eine Langzeitblutdruckmessung. Lokalisationsdiagnostik und Metastasensuche (10% der Phaochromozytome sind maligne) erfolgt durch Sonographie, CT oder MRT, zum Ausschluss extraadrenaler Manifestationen dient die MIBG (123Iod-Metaiodobenzylguanidin)-Szintigraphie. Auszuschliesen sind assoziierte Syndrome (MEN2-, Von-Hippel-Lindau-Syndrom). Die definitive Therapie ist chirurgisch, zur Vorbereitung erforderlich ist eine α-Adrenorezeptor-Blockade, erst danach darf ein β-Adrenorezeptorblocker appliziert werden.

Kidney transplantation is the best option for all patients with terminal renal failure. Kidney transplantation is not only associated with an improved quality of life in comparison to all other renal replacement therapies, this method also offers a significantly extended lifespan. Therefore, the option for transplantation has to be verified for every patient with renal failure. Graft and patient survival is best when transplantation is carried out just before starting dialysis treatment. Realistically, only living donor transplantation offers the option of sparing the recipient a long waiting period on dialysis. Although transplantation from living donors is superior to cadaveric kidney transplantation, a small risk remains for the donor. Kidney transplantation and the immunosuppressive therapy are associated with an increased risk for certain types of infection, an increased tumour risk and an increased risk for cardiovascular complications. To address these problems, specific recommendations for patient surveillance have been provided by different transplantation societies.

Die medikamentose Immunsuppression nach Organtransplantation ist mit einem erhohten Risiko verbunden, an opportunistischen Infektionen zu erkranken. Durch die Modulation des Immunsystems sind die klinische Symptomatik, der Verlauf und typische diagnostische Zeichen wie Rontgenbildveranderung, Fieber oder Blutbildveranderungen modifiziert. Trotzdem bedurfen gerade diese Patienten einer schnellen Diagnosestellung und der fruhzeitigen Einleitung der Therapie. Dies gelingt nur, wenn selbst primar blande erscheinende Symptome bei dieser Patientengruppe richtig interpretiert werden und eine konsequente Diagnostik zur Folge hat. Hierfur bedarf es einer verbreiteten Kenntnis dieser Erkrankungen und einer engen Zusammenarbeit zwischen niedergelassenen Internisten und dem Transplantationszentrum.

The risk to acquire opportunistic infections is clearly increased in patients receiving immunosuppressive therapeutic regimens following organ transplantation or during treatment of autoimmune disorders. The modulation of the immune system can alter the clinical symptoms and the course of infectious diseases, including diagnostic signs such as fever or pathological changes in radiographs or blood cell counts. However, a rapid diagnosis and start of treatment is essential in these patients. Thus, a correct interpretation of even mild symptoms in the initial phase of an infectious disease is essential for establishing a diagnosis and initiation of a therapy at an early stage. Therefore, it is necessary that the clinical hallmarks of these diseases are widely known and that physicians treating these patients cooperate closely with transplant centers.

Objective: Therapy of elevated cholesterol serum concentrations is often necessary in patients with kidney transplants. However, the pharmacokinetics of HMG-CoA reductase inhibitors when administered in combination with sirolimus and cyclosporin A (CsA) have not been determined. The aim of this study was to investigate the pharmacokinetics of cerivastatin when administered in combination with sirolimus in patients with kidney transplants, and to review the literature with regard to the differences in pharmacological behavior between sirolimus, CsA and tacrolimus. Methods: Patients (n = 7) with a stable and functioning kidney transplant and elevated LDL cholesterol serum concentrations were included in the study. After an observation period of 3 months, and whilst receiving sirolimus and CsA, cerivastatin (0.2 mg daily) was administered for a period of 3 months. Pharmacokinetic parameters were calculated on Day 1 and 3 months after initiation of cerivastatin therapy. Routine laboratory parameters and clinical adverse events were monitored throughout the study period. Results: Single-dose cerivastatin AUC was 2 to 3-fold higher in comparison to published values obtained in healthy subjects. The accumulation ratio of cerivastatin (after 3 months/ Day 1) was 1.6. Sirolimus and CsA trough levels, and the sirolimus AUC did not differ after single dose and multiple doses of cerivastatin. Conclusions: The combination therapy of cerivastatin with sirolimus and CsA leads to a significant increase in cerivastatin exposure. Additional drug monitoring of sirolimus and CsA is not necessary.

Acute interstitial nephritis has been known as a complication of mainly streptococcal infection for nearly a century. With the advent of infection control, it became a complication caused by antibiotics and later by other drugs, which might have changed the outcome. To determine risk factors for the development of chronic renal insufficiency, and thus, the transition from acute to chronic interstitial nephritis, we performed a retrospective study of all cases of acute interstitial nephritis found by reviewing 1,068 renal biopsies from 1968 to 1997.Patients with permanent and reversible renal insufficiency after acute interstitial nephritis were compared with respect to the causative event, the symptoms, and the clinical and histological findings. Differences between the groups were calculated by applying bi- and multivariate analysis.Acute interstitial nephritis was found in 6.5% of all biopsies (64 patients with 68 episodes of acute interstitial nephritis); it was infection-induced in 10%, idiopathic in 4%, and drug-induced in 85% of the cases (antibiotics in 13 cases, analgesics in 17, non-steroidal anti-inflammatory drugs (NSAIDs) in 16, diuretics in 5, and various other drugs in 7). Renal insufficiency was reversible in 69% and permanent in 31% (12% partially reversible, 19% irreversible). The infection-induced and idiopathic types of acute interstitial nephritis were always reversible. Drug-related acute interstitial nephritis caused permanent renal insufficiency in 36% with a maximum of 56% in NSAID-induced cases. In drug-induced cases, intake of the suspected drug for more than a month prior to diagnosis caused permanent renal insufficiency in 88% and interstitial granuloma in 31%. Multivariate analysis disclosed the following significant features separating the permanent from the reversible renal insufficiency group: patients in the first group had more tubular atrophy in their histology, more chronic use of mixed analgesics and/or NSAIDs, less oliguria or anuria as an acute symptom, fewer antibiotics as causative agents, more interstitial granuloma, more pronounced interstitial cell infiltration in their histology, and more imaging of renal shrinkage. Renal histology had the highest predictive value.Today, acute interstitial nephritis is mainly drug-induced. NSAIDs are the most frequent cause of permanent renal insufficiency after acute interstitial nephritis. Clinically, subacute symptoms, a prolonged intake of the suspect drug, and chronic analgesic or NSAID use are related to a more chronic course of interstitial nephritis. In histology, tubular atrophy, interstitial granuloma, and pronounced interstitial cell infiltration indicate chronicity.

Cell-mediated immune responses can be down-regulated by induction of apoptosis of immunoreactive lymphocytes. In the present study, we have tested the feasibility of a strategy for immunosuppression by the selective induction of apoptosis in activated, interleukin (IL)-2 receptor-positive lymphocytes, using a triple IL-2-IgG-FasL fusion protein. The IL-2-IgG-FasL fusion protein combines IL-2 for the selection of activated T cells, with the extracellular domain of the FasL molecule for inducing T-cell apoptosis. These components were separated by the Fc part of IgG1 serving as a spacer as well as for half-life prolongation.The gene for the chimeric protein was created by fusing DNA sequences encoding for the three functional components: human IL-2, the Fc part of human IgG1, and the extracellular domain of murine FasL. When the fusion gene was expressed in murine J558L cells, we obtained soluble dimeric immunoglobulin-like proteins in the supernatant. After analyzing the function of the IL-2 and FasL portions individually in vitro, a delayed-type hypersensitivity (DTH) reaction to sheep red blood cells as model for cell-mediated immune responses was investigated to evaluate the IL-2-IgG-FasL-mediated immunosuppression in vivo.In vitro, the IL-2-IgG-FasL fusion protein supported IL-2-dependent proliferation of Fas-resistant CTLL-2 cells, whereas concanavalin A-T blasts were induced to undergo apoptosis by the FasL portion. In vivo, this fusion protein potently inhibited a murine DTH. This was associated with an increased rate of apoptosis in activated lymphocytes in the spleen, even at very low doses of the fusion protein. Furthermore, a second antigen challenge 10 days after IL-2-IgG-FasL treatment still failed to elicit a DTH response.The abrogation of a standard T cell-dependent immune response in vivo demonstrates that IL-2-IgG-FasL can be successfully exploited to trigger the death of deleterious T cells, presenting a potentially useful strategy in the management of autoimmune diseases and allotransplant rejections.

Here we provide proof that the injection of tumor cells engineered to secrete interleukin 2 (IL-2)-IgG chimeric proteins locally induces potent antitumor responses, which are more effective than tumor transfection with IL-2 alone. Murine plasmacytoma cells (J558L) were stably transfected with DNA coding for a human IL-2-IgG1 or a murine IL-2-IgG2b fusion protein and were injected s.c. into syngeneic BALB/c mice. Evaluation of tumor growth and rejection patterns showed that IL-2-IgG secretion by transfected J558L tumor cells induced their rejection in all animals tested, similar to the rejection of J558L cells engineered to secrete IL-2 alone, whereas treatment with parental cells was lethal. However, mice treated with IL-2-IgG-secreting J558L cells (human IL-2-IgG1 and murine IL-2-IgG2b) exhibited a significantly stronger tumor immunity against a later challenge with parental J558L cells than mice treated with IL-2-secreting tumor cells.

Lymphocyte binding to endothelial surface adhesion molecules is an important early step in inflammation, which is mediated initially by P-selectin and E-selectin. We tested the hypothesis that lymphocyte binding to the selectin adhesion molecules induces intracellular signaling by tyrosine phosphorylation. We used an adhesion assay, which relied on cell binding to chimeric proteins consisting of the extracellular domains for P-selectin and E-selectin. Tyrosine phosphorylation was determined using anti-phosphotyrosine Abs by confocal microscopy and Western blot. Binding to P-selectin induced a significant increase in anti-phosphotyrosine immunoreactivity. The P-selectin effect was time dependent with an early response after 10 min and a maximum effect at 30 min. Western blot showed a time-dependent phosphorylation of two distinct 68- and 125-kDa proteins. These proteins were pp125 focal adhesion kinase (FAK) and paxillin, as shown by immunoprecipitation and colocalization. Phosphorylation of pp125 FAK was time dependent reaching a maximum after 30 min. Incubation with the tyrosine kinase inhibitor genistein, and, to a lesser extent, with the protein kinase C inhibitor staurosporine, resulted in decreased pp125 FAK phosphorylation. Our results are the first to demonstrate that lymphocyte binding to P-selectin induces tyrosine phosphorylation of distinct proteins. Thus, lymphocyte activation may occur already at the initial contact with surface adhesion molecules.