title: Aberrant regulation of polymorphonuclear phagocyte responsiveness in multitrauma patients.
abstract: A systemic inflammatory response often follows severe trauma. Priming (preactivation) of polymorphonuclear phagocytes (PMNs) is an essential first step in the processes that lead to damage caused by the systemic activation of innate immune response. Until recently, priming could only accurately be measured by functional assays, which require isolation of cells, thereby potentially inducing artificial activation. The aim of this study was to identify primed PMNs in response to trauma by using a whole blood analysis with a broad detection range. Twenty-two trauma patients were analyzed for PMN priming with novel developed antibodies recognizing priming epitopes by flow cytometric analysis. Expression of priming epitopes on PMNs was analyzed with respect to time, injury, and disease severity. Expression of priming epitopes in the circulation was compared with expression profiles of PMNs obtained from lung fluid. Fourteen healthy volunteers served as controls. Expression of priming epitopes on peripheral blood PMNs of injured patients was similar, as found in healthy controls, whereas highly primed cells were found in the lung fluid of injured patients (increase of >50 times as compared with peripheral blood cells). In fact, the responsiveness of PMNs toward the bacteria-derived stimulus N-formyl-methionyl-leucyl-phenylalanine was markedly decreased in trauma patients. Lack of expression of priming epitopes and the unresponsiveness to N-formyl-methionyl-leucyl-phenylalanine demonstrates the presence of partially refractory cells in the circulation of trauma patients. An increased expression of epitopes found on pulmonary PMNs suggests that optimal (pre)activation of these cells only occurs in the tissues.
authors.affiliation: Department of Surgery, University Medical Centre Utrecht, 3508 GA Utrecht, The Netherlands. F.Hietbrink@umctrecht.nl
authors.forename: Falco
authors.initials: F
authors.lastname: Hietbrink
authors.forename: Erik-Jan
authors.initials: EJ
authors.lastname: Oudijk
authors.forename: Reinier
authors.initials: R
authors.lastname: Braams
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
authors.forename: Luke
authors.initials: L
authors.lastname: Leenen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry; D002467:Cell Nucleus / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010586:Phagocytes / Q000378:metabolism*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000097:blood*
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes