Abstract 5

Adhaesion molecules mediate various adhaesion steps (rolling, firm adhaerence, extravasation). Neonatal PMN demonstrate decreased adhaerence, spreading and degranulation compared with adults. Abnormalities of motile functions are more severe in premature infants than in full-term neonates. Soluble selectins (responsible for rolling) show a positive correlation to the gestational age. Leukocytes must deform markedly to pass through narrow capillaries with diameters of about 5 mm. Mature PMN have four times larger volume and 500 times higher flow resistance through marrow capillaries than erythrocytes. Fortunately, leukocytes usually travel through relatively wide capillaries with high flow, thereby requiring little or no deformation. At low perfusion pressure, however, leukocytes enter into narrow capillaries with low flow and obstruct these vessels, thereby further deteriorating flow through ischemic tissues. A major role of PMN accumulation in the development of hypoxic-ischaemic organ damage has been shown in adult and neonatal animal models. Leukocyte adhaesion deficiency in animals ("knock-out" mouse) and humans may be associated with impaired inflammatory response.

Research on adhaesion and rheology of leukocytes may focus on peculiarities in the healthy fetus and neonate, on mechanisms and therapeutic approaches in bacterial infections, ischaemia and reperfusion injury, pulmonary disorders (BPD, asthma), retinopathy, diabetes, graft rejection, leukaemias, metastasis etc. Effects of several anti-adhaesion agents are presently studied (e.g. anti ICAM-1 Mab). Moreover, pentixiphylline may prevent activation and rigidification of neutrophils.