Neutrophil dysfunction in sepsis. III. Degranulation as a mechanism for nonspecific deactivation.
Prominent and global abnormalities in chemotactic, oxidative, and microbicidal activity have been identified in neutrophils from patients with severe sepsis. To evaluate the possible contribution of degranulation as the basis for the observed abnormalities, 12 patients with intrabdominal infection were serially studied and neutrophil chemotaxis, enzyme content, and receptors for FMLP were evaluated. There was a significant correlation between chemotactic response to both activated serum and FMLP with the granular enzymes beta-glucuronidase and lysozyme. For FMLP-directed migration, r = 0.73, P less than 0.001 for lysozyme, and r = 0.59, P less than 0.001 for beta-glucuronidase. There was a similarly significant correlation between loss of lysozyme and an increase in FMLP receptors, previously shown to be a marker for degranulation. These data support the concept that in vivo degranulation, possibly due to effects of circulating chemoattractants on adherent neutrophils, is responsible for the enzymatic and chemotactic loss seen in cells from septic patients. This hypothesis also provides a mechanism to explain the respiratory distress syndrome if degranulation were to occur in the pulmonary capillary bed.
D001424:Bacterial Infections / Q000097:blood*; D001660:Biliary Tract Diseases / Q000097:blood*; D002634:Chemotaxis, Leukocyte; D003108:Colonic Diseases / Q000097:blood; D003594:Cytoplasmic Granules / Q000502:physiology*; D004378:Duodenal Diseases / Q000097:blood; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D007410:Intestinal Diseases / Q000097:blood*; D009113:Muramidase / Q000097:blood; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000097:blood; D009504:Neutrophils / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D044042:Receptors, Formyl Peptide
D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009113:Muramidase; D005966:Glucuronidase