Transient absence of C5a-specific neutrophil function in inflammatory disorders of the skin.
Chemotactic migration, production of superoxide anion (O2-), and the release of beta-glucuronidase from azurophilic granules were determined in polymorphonuclear leukocytes (PMN) from 135 patients with infectious (e.g., pyoderma, acne conglobata, erysipelas) as well as noninfectious (psoriasis) skin diseases. Purified C5a and the formylated tripeptide FMLP were used as stimuli. In addition, longitudinal profiles of PMN activities were performed at daily intervals in several patients. There was a complete absence of PMN responses (chemotaxis, O2--production, and enzyme release) specifically induced by C5a in 25 patients suffering from various inflammatory diseases of the skin. In these patients PMN responsiveness for the tripeptide FMLP was either normal or increased. The C5a-dependent defect of PMN was transient and correlated with disease activity. When normal PMN were incubated with sera from C5a-defective patients, no inherent stimulatory or inhibitory activities compared to control sera were seen. Pretreatment of normal PMN in vitro with various concentrations of C5a failed to completely deactivate PMN without affecting FMLP dependent functions. These observations demonstrate the presence of a functional defect in circulating PMN during acute cutaneous inflammation. The in vitro experiments suggest transient blocking of C5a-dependent PMN functions by a cell-bound factor which seems not to be C5a or C5adesarg.
Schröder
J M
JM
Christophers
E
E
D000152:Acne Vulgaris / Q000175:diagnosis / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D003182:Complement C5 / Q000502:physiology*; D015936:Complement C5a; D003872:Dermatitis / Q000276:immunology*; D004886:Erysipelas / Q000175:diagnosis / Q000276:immunology; D006801:Humans; D008137:Longitudinal Studies; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D011565:Psoriasis / Q000175:diagnosis / Q000276:immunology; D011711:Pyoderma / Q000175:diagnosis / Q000276:immunology; D014581:Urticaria / Q000175:diagnosis / Q000276:immunology
D003182:Complement C5; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a