Postnatal maturation of total cell content and up-regulated surface expression of Mac-1 (CD11b/CD18) in polymorphonuclear leukocytes of human infants

Abstract

Markedly deficient expression of membrane-activated complex 1 (Mac-1; CD11b/CD18) by polymorphonuclear neutrophils (PMN) of human neonates compared with adults is well documented. To define postnatal maturation of Mac-1 expression of PMN, lysates of PMN from 21 infants, aged 1-14 months, and concurrent adult controls were assayed by ELISA for total cell content of Mac-1 and LFA-1 (CD11a/CD18), and LFA-1 content was within the normal adult range at all ages tested. Mac-1 content was approximately 50% of adult levels for infants 1-2 months of age and steadily increased to reach normal adult levels by 11-12 months of age. For a separate group of 25 infants, aged 0.5-11 months, measurement of surface expression of Mac-1 and LFA-1 on activated PMN by immunofluorescence flow cytometry yielded results that were similar to those obtained by ELISA.

Leukocyte recruitment in preterm and term infants

“…Similar observations have been described for other adhesion molecules such as ICAM-1/-2, VCAM-1, VLA4, and PSGL-1 [29, 31, 38, 39]. Although fetal expression of the majority of adhesion molecules is low when compared to term infants and adults [11, 26, 36], others, like CXCR2, PECAM-1, and VE-cadherin (and LFA-1), are equally expressed in premature and mature neonates and adults (Table 2) [29, 31, 37]. …”

“…After extravasation, the neutrophil follows chemokine gradients through the tissue to the point of damage/inflammation. Developmental alterations of adhesion molecule expression are indicated by footnotes as follows (fetal/premature levels were compared to those of adults): ( a ) L-selectin - reduced [26, 33, 37, 45, 46] and unchanged [47], E-selectin - reduced [29, 31, 38], P-selectin - reduced [29, 34, 38, 39]; ( b ) PSGL-1 - reduced [29, 31, 36]; ( c ) Mac-1 - reduced [26, 31, 36], unchanged [30, 33], and increased [37]; ( d ) LFA-1 - reduced [26, 45] and unchanged [30, 31, 36, 37]; ( e ) ICAM-1 - reduced [29, 31, 38]; ( f ) CXCR2 - unchanged [31] …”

“…On the other hand, posttranslational glycosylation of selectin ligands is augmented during the neonatal period [35]. In most studies, fetal expression of integrins such as Mac-1 and LFA-1 were described to be reduced or equal compared to adults [26, 30, 31, 33, 36, 37]. Similar observations have been described for other adhesion molecules such as ICAM-1/-2, VCAM-1, VLA4, and PSGL-1 [29, 31, 38, 39].…”

Neutrophil and endothelial adhesive function during human fetal ontogeny

“…By contrast, LFA-1 was already expressed early during gestation and did not change with advancing maturation of the fetuses. Despite being reported consistently, the nature of this difference remains elusive [24,31,35]. It has been known for a long time that integrin expression is regulated differentially in a cell-and development-specific manner [37].…”

Inflammatory responses in hypoxic ischemic encephalopathy

“…To form a firm adhesion, integrins must bind to counter-receptors of the immunoglobulin superfamily expressed on inflamed endothelial cells, including ICAM-1, ICAM-2, VCAM-1, the mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), platelet-endothelial cell adhesion molecule-1 (PECAM-1), and the receptor for advanced glycation end products (RAGE) 101,102,103 . Although no age-related differences in basal and stimulated LFA-1 surface expression were found in human neonatal and adult neutrophils 104,105,106,107,108 , Mac-1 expression remains low during the prenatal and postnatal periods and reaches adult levels by 11 months 108,109 . The lower surface expression of Mac-1 on neonatal neutrophils has been directly linked to impaired transendothelial migration under chemotactic stimulation 75,110 (Table 1).…”