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 (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.(ABSTRACT TRUNCATED AT 250 WORDS)
Tschaikowsky
K
K
Institut für Anaesthesiologie, Universität Erlangen-Nürnberg.
Sittl
R
R
Braun
G G
GG
Hering
W
W
Rügheimer
E
E
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002634:Chemotaxis, Leukocyte; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D018000:Receptors, Peptide / Q000096:biosynthesis*; D016897:Respiratory Burst; D012772:Shock, Septic / Q000378:metabolism* / Q000473:pathology; D013481:Superoxides / Q000378:metabolism*; D014947:Wounds and Injuries / Q000378:metabolism* / Q000473:pathology
D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine