Increased fMet-Leu-Phe receptor expression and altered superoxide production of neutrophil granulocytes in septic and posttraumatic patients

Activation of neutrophils by various inflammatory stimuli has been shown to play a pivotal role in septic and posttraumatic tissue injury. To further elucidate the mechanisms modulating the oxidative metabolism, we assessed superoxide production induced by N-formylmethionyl-leucyl-phenylalanine (FML...

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Bibliographic Details
Published in:The Clinical Investigator 1993-12, Vol.72 (1), p.18-25
Main Authors: TSCHAIKOWSKY, K, SITTL, R, BRAUN, G. G, HERING, W, RÜGHEIMER, E
Format: Article
Language:English
Subjects:
Adult
Aged
Amino Acid Sequence
Biological and medical sciences
Chemotaxis, Leukocyte
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Immunobiology
Male
Middle Aged
Molecular Sequence Data
Myeloid cells: ontogeny, maturation, markers, receptors
N-Formylmethionine Leucyl-Phenylalanine - metabolism
Neutrophils - metabolism
Polynuclears
Receptors, Formyl Peptide
Receptors, Immunologic - biosynthesis
Receptors, Peptide - biosynthesis
Respiratory Burst
Shock, Septic - metabolism
Shock, Septic - pathology
Superoxides - metabolism
Wounds and Injuries - metabolism
Wounds and Injuries - pathology
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Summary:Activation of neutrophils by various inflammatory stimuli has been shown to play a pivotal role in septic and posttraumatic tissue injury. To further elucidate the mechanisms modulating the oxidative metabolism, we assessed superoxide production induced by N-formylmethionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate and the expression of FMLP receptors of human neutrophils on several days during sepsis and after trauma. Neutrophils of septic patients isolated on days 0-4 after the diagnosis of sepsis showed a significant, more than twofold increase in specific binding of [3H]FMLP at 1, 120, and 240 nM. Scatchard plot analyses revealed that this increase in specific binding was due to an increase in the number of low- and high-affinity FMLP receptors with no changes in receptor affinity. On days 5-10 after the onset of sepsis the up-regulation of FMLP receptors on circulating neutrophils was followed by receptor down-regulation. Likewise, neutrophils from patients with trauma that was not complicated by sepsis bound significantly more [3H]FMLP than neutrophils from volunteers. However, the increase in FMLP receptors was less than that in septic neutrophils and returned earlier to normal. In accordance with the up-regulation of FMLP receptors, neutrophils obtained from patients with sepsis or after trauma on days 1-4 and days 1-2, respectively, produced significantly more superoxide anion upon stimulation with FMLP. However, after stimulation with phorbol myristate acetate, a receptor-independent activator of protein kinase C, these cells released less superoxide anion than controls.
ISSN:0941-0198
1432-1440
DOI:10.1007/bf00231111