Diversity in regulation of adhesion molecules

The surface expression and regulation of the adhesion promoting glycoproteins Mac-i and L-selectin was measured on monocytes and neutrophils from neonates and adults. A significant decrease in Mac-I up regulation on both monocytes and neutrophils was found in neonates after both high (10-7M) and low (10-9M) concentrations of the chemotactic factor N-formyl-methionyl-phenylalanine (FMLP). A significant difference was obtained after incubation for five minutes, which was further enhanced after incubation for 15 minutes. Factors related to bacterial infections, lipopolysaccharides, activated sera (C5a), and aggregated IgG induced an impaired Mac-I up regulation on both monocytes and neutrophils from neonates compared with adults. The expression of L-selectin was significantly lower on neutrophils from neonates and was less down regulated upon stimulation with a low concentration (10-12M) of FMLP. On monocytes from neonates, the expression and down regulation of Lselectin did not differ from monocytes from adults. Mode of delivery did not influence the regulation of Mac-i and Lselectin in neonates. Diversity in expression and regulation ofMacI and L-selectin on monocytes and neutrophils may contribute to the increased susceptibility to infections observed in neonates. (Arch Dis Child 1993; 68: 561-565) Karolinska Hospital, S-10401, Stockholm, Sweden, Department ofPaediatrics C Torok H Lagercrantz Department of Clinical Immunology J Lundahl J Hed Correspondence to: Dr Lundahl. Accepted 14 December 1992 The immunological host defence is immature in the human neonate, which may contribute to the high incidence of overwhelming sepsis in preterm and term infants.' The most consistent defect described is the inability of the neonatal neutrophils to accumulate at the site of bacterial invasion.2 This is partly due to a reduced neutrophil storage pool and a failure to increase the stem cell proliferation rate during sepsis.3 4 Previous studies have revealed that neutrophils from neonates have impaired adherence to and migration through endothelium and also impaired chemotaxis.5-8 Immaturity in other defence systems9 such as decreased opsonic activity9 10 can contribute to the increased infection rate. During acute inflammation, neutrophils and monocytes are recruited to the inflammatory site.-1 13 Neutrophils are important effector cells during bacterial infections and monocytes undergo maturation to inflammatory macrophages performing both immune and non-immune functions.'3 14 Both neutrophils and monocytes pass several transient attachments to the vessel walls before the final adhesion to and transmigration through the endothelium.15-17 This recruitment is regulated by a sequential interaction of different adhesion molecules. Two important families of adhesion molecules are involved in this recruitment and are designated selectins and integrins. Selectins mediate the first step of attachment to endothelium; this is called 'rolling'. 18-20 This rolling preceeds a firm adhesion that is mediated by the integrin family.'5 16 L-Selectin is distributed on most leucocytes and is down regulated upon stimulation with chemotactic factors.2' 22 Mac-i is an important adhesion molecule in the integrin family that mediates firm adhesion to endothelium. Upon stimulation with chemotactic factors, Mac-1 is rapidly mobilised to the surface from an intracellular pool.23-25 This inverse regulation of L-selectin and Mac-i is a prerequisite for the sequential interaction between inflammatory cells and endothelium leading to an inflammatory response. The aim of the present study was to see whether immaturity of expression and regulation of these adhesion molecules on monocytes and neutrophils could predispose to severe infection in the infant.