Role of Chemotactic Factors in Neutrophil Activation After Thermal Injury in Rats

Byline: Maria-Thereza S. Piccolo (1,4), Yun Wang (1), Serge Verbrugge (2), Roscoe L. Warner (1), Paulina Sannomiya (3), Nelson S. Piccolo (4), Monica S. Piccolo (4), Tony E. Hugli (5), Peter A. Ward (1), Gerd O. Till (1) Abstract: Acute thermal trauma is well known to produce evidence of a 'systemic inflammatory response' in vivo, as manifested by evidence of complement activation, appearance in plasma of a variety of inflammatory factors, and development of multi-organ injury. The current studies were focused on acute thermal injury of rat skin and factors responsible for accompanying activation of blood neutrophils. Acute thermal injury of rat skin resulted in a time-dependent loss of L-selectin and up-regulation of Mac-1 (CD11b/CD18) on blood neutrophils, with no changes in LFA-1 (CD11a/CD18). The loss of L-selectin was prevented by blockade of C5a but not by blockade of the [alpha]-chemokine, macrophage inflammatory protein-2 (MIP-2). C5a, the [alpha] chemokines, MIP-2 and keratinocyte-derived cytokine (KC), and platelet activating factor (PAF) contributed to up-regulation of blood neutrophil Mac-1. Blocking interventions against these mediators also blunted the degree of neutropenia developing after thermal trauma. These data suggest that activation of blood neutrophils after thermal trauma is related to the role of several chemotactic mediators. These studies may provide clues regarding factors responsible for development of the 'systemic inflammatory response syndrome' after thermal injury in the experimental model employed. Author Affiliation: (1) Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, 48109 (2) Department of Experimental Anesthesiology, Erasmus University of Rotterdam, Rotterdam, The Netherlands (3) Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (4) Pronto Socorro para Queimaduras, Goiania-GO, Brazil (5) Division of Immunology, Scripps Research Institute, La Jolla, California, 92037 Article History: Registration Date: 30/09/2004