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Fibrotic reactions in the skin are frequently preceded by infiltration of inflammatory cells and subsequent migration of fibroblastic cells. Interleukin-1 is secreted by inflammatory cells and can regulate proliferation and protein synthesis of fibroblasts. Its role in fibroblast chemotaxis has not been elucidated in any detail. Using the well-established Boyden chamber assay for measurement of chemotaxis in vitro, we studied a wide range of recombinant human interleukin-1α concentrations to assess intrinsic chemotactic activity of interleukin-1α and to determine the capacity of this mediator to modify the chemotactic response of fibroblasts to other chemoattractants. This was compared with the interleukin- la dose required for enhancement of mRNA expression for collagenase. Although interleukin-1α was not chemoattractive for fibroblasts, it specifically augmented migration toward fibroblast-conditioned medium and toward platelet- derived growth factor but not toward epidermal growth factor, fibronectin, or transforming-growth factor-β. Interleukin-1α did not measurably alter the expression of mRNA for the platelet-derived growth factor receptor or its platelet-derived growth factor-binding characteristics. Doses required to enhance fibroblast chemotaxis were distinctly lower than those required for stimulation of collagenase mRNA expression. [ABSTRACT FROM AUTHOR]

Collagen immunofluorescence studies were performed on biopsy specimens from 25 patients with cryptogenic fibrosing alveolitis. We studied the relationship of these results to the clinical, radiological, and physiological assessments of disease activity during six-month periods before and after the lung biopsy; to the appearances on routine histological examination; to the inflammatory cell proportions in bronchoalveolar lavage fluid; and to the response to treatment. Positive associations were observed between the presence of type III collagen and disease activity before (p less than 0.015) and after (p less than 0.02) lung biopsy. These were independent of clinical and routine histological features. The type-III-positive group also contained nine of the 11 responding to treatment. None of the type-III-positive patients had a quiescent or stable course. In contrast, most patients with no type-III-collagen fluorescence had a stable course over the time of this study and did not improve on treatment. It is suggested that collagen typing may be an additional useful method of assessing potentially reversible disease in cryptogenic fibrosing alveolitis. [ABSTRACT FROM AUTHOR]

Highly purified type-specific anti-collagen antibodies (prepared in animals to types I, II, III, and IV bovine collagen) were used in an indirect immunofluorescence method for the study of human lung collagen. The tissue localisation of each collagen type, and the apparent type I:III collagen ratio was assessed in normal foetal and adult lung and in fibrotic lung lesions. In the latter, the relationship of the findings to the natural history of the lesion was considered. This method was compared with routine connective tissue stains. The following observations were made. (1) Foetal lung in the canalicular phase of development proved a useful substrate for validating and standardizing the procedure. (2) Collagen fluorescence was more sensitive than connective tissue stains in detecting collagen in foetal tissues and sites of early fibrosis. (3) On the basis of collagen-type fluorescence, two distinctive patterns of fibrosis were recognised. Areas of mature collagen surrounding vessels and bronchi and in established scar tissue, for example in asbestotic pleural plaques, were virtually exclusively type I collagen. By contrast, areas of early active fibrosis like sarcoid nodules and organising pneumonia, which usually contained variable numbers of fibroblasts and chronic inflammatory cells, were characterised by an increased proportion of type III collagen and a greater intensity of both types I and III collagen fluorescence. The possible significance of this change in type III:I collagen ratio is discussed. Determination of the stage of fibrotic lesions by this method might have applications in the prediction of disease progression, and influence management of some conditions. [ABSTRACT FROM AUTHOR]

In order to establish criteria for selection of the best ova in in-vitro fertilization-embryo transfer (IVF-ET) programes we have examined the follicular fluid (FF) levels of plasminogen activator (PA), collagenolytic activity, progesterone (P) and alpha 2 macroglobulin (alpha 2M) and related them to the success of pregnancy. PA activity was similar in FF of pregnant and nonpregnant cycles, 13.8 +/- 3.9 mU/ml versus 14.6 +/- 2.9 (mean +/- SEM) respectively. By contrast, FF from pregnant cycles exhibited lower collagenolytic activity (49.6 +/- 3.9% versus 67.9 +/- 3.0; P less than 0.001). Likewise, in a semi-quantitative assay of alpha 2M, only 18.4% of the aspirates from pregnant cycles showed a precipitation line, whereas 76.8% of those from non-pregnant cycles were positive. Levels of P in aspirates from pregnant cycles were in the intermediate range, as compared with those from non-pregnant cycles (0.06-5.5 micrograms/ml versus 0.02-12.0 micrograms/ml). All these assays can be completed before ET and performed in IVF-ET programmes. In conclusion, it seems that a combination of follicular alpha 2M levels and collagenolytic activity, and to a lesser extent addition of P assay, may serve as good criteria for selecting the best embryos for establishment of pregnancy. [ABSTRACT FROM AUTHOR]