title: Subcellular distribution and mobilization of MAC-1 (CD11b/CD18) in neonatal neutrophils.
abstract: The CD11b/CD18 (Mac-1) heterodimeric surface glycoprotein contributes to a broad range of adherence-dependent neutrophil inflammatory functions. Previous investigations have indicated that diminished expression or regulation of Mac-1 may underlie abnormalities of stimulated adhesion and chemotaxis of neonatal neutrophils in vitro and inflammatory deficits in human neonates. To define the pathogenic mechanisms contributing to these findings, we compared the distribution and translocation of Mac-1 in subcellular fractions of neonatal and adult neutrophils before and after chemotactic stimulation. The total cell content of Mac-1 and the proportions of Mac-1 in beta fractions (vitamin B12 binding protein-rich granules), pre-gamma fractions (gelatinase-rich granules), or gamma fractions (plasma membrane) of neonatal neutrophils were comparable with those of adult neutrophils. However, after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10 nmol/L, 37 degrees C, 15 minutes), neonatal neutrophils demonstrated (1) diminished translocation of Mac-1 from pre-gamma fractions (P less than .05), and (2) diminished surface expression of Mac-1 (P less than .05), as compared with healthy adult neutrophils. As shown in enzymatic and immunochemical assays, neonatal cells contained significantly (P less than .01) diminished levels of neutrophil gelatinase. In response to FMLP (0.1 to 10 nmol/L, 37 degrees C, 15 minutes), neonatal suspensions also released significantly (P less than .001) less gelatinase, as compared with adult neutrophil suspensions. These observations demonstrate that diminished mobilization of Mac-1 from gelatinase-rich granular pools in neonatal neutrophils is associated with abnormal surface expression of this glycoprotein after chemotactic stimulation. This abnormality may contribute, in part, to abnormal migratory properties of neonatal neutrophils in response to inflammatory stimuli.
authors: Department of Pediatrics, Microbiology and Immunology, and Cell Biology, Baylor College of Medicine, Speros P. Martel Leukocyte Biology Laboratory, Texas Children's Hospital, Houston.
authors: D H
authors: DH
authors: Jones
authors: F C
authors: FC
authors: Schmalstieg
authors: K
authors: K
authors: Dempsey
authors: S S
authors: SS
authors: Krater
authors: D D
authors: DD
authors: Nannen
authors: C W
authors: CW
authors: Smith
authors: D C
authors: DC
authors: Anderson
mesh_terms: D000943:Antigens, Differentiation / Q000378:metabolism*; D001692:Biological Transport; D002451:Cell Compartmentation; D002634:Chemotaxis, Leukocyte; D003594:Cytoplasmic Granules / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D018093:Gelatinases; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D007781:Lactoferrin / Q000378:metabolism; D016177:Macrophage-1 Antigen; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D010434:Pepsin A / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014155:Transcobalamins / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D016177:Macrophage-1 Antigen; D016028:Receptors, Leukocyte-Adhesion; D014155:Transcobalamins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007781:Lactoferrin; D010434:Pepsin A; D018093:Gelatinases; D013755:Tetradecanoylphorbol Acetate