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Subcellular distribution and mobilization of MAC-1 (CD11b/CD18) in neonatal neutrophils
D H Jones1, F C Schmalstieg, K Dempsey
1Department of Pediatrics, Microbiology and Immunology, and Cell Biology, Baylor College of Medicine, Speros P. Martel Leukocyte Biology Laboratory, Texas Children's Hospital, Houston.
Insights
Neonatal neutrophils show impaired Mac-1 glycoprotein mobilization from internal stores, leading to reduced surface expression and abnormal inflammatory responses. This impacts neutrophil adhesion and migration in newborns.
Area of Science:
- Immunology
- Cell Biology
- Neonatal Research
Background:
- The CD11b/CD18 (Mac-1) glycoprotein is crucial for neutrophil inflammatory functions.
- Previous studies suggest Mac-1 regulation issues in neonatal neutrophils may cause inflammatory deficits.
Purpose of the Study:
- To investigate the pathogenic mechanisms behind abnormal Mac-1 distribution and translocation in neonatal neutrophils.
- To compare Mac-1 behavior in neonatal versus adult neutrophils post-stimulation.
Main Methods:
- Compared subcellular distribution and translocation of Mac-1 in neonatal and adult neutrophils.
- Utilized chemotactic stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP).
- Assessed neutrophil gelatinase levels via enzymatic and immunochemical assays.
Main Results:
- Neonatal neutrophils exhibited diminished Mac-1 translocation from pre-gamma fractions and reduced surface expression after FMLP stimulation compared to adults.
- Neonatal neutrophils contained significantly lower levels of neutrophil gelatinase.
- FMLP stimulation resulted in significantly less gelatinase release from neonatal neutrophil suspensions.
Conclusions:
- Diminished Mac-1 mobilization from gelatinase-rich granules in neonatal neutrophils is linked to abnormal surface expression after chemotactic stimulation.
- This Mac-1 mobilization defect may contribute to the abnormal migratory properties of neonatal neutrophils.
- Understanding these mechanisms is vital for addressing neonatal inflammatory deficits.
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.
