Host Defense Deficiency in Newborn Nonhuman Primate Lungs

Current evidence indicates that the localization and extravasation of neutrophils is a complex process involving several adhesion molecules with apparently distinct functions, and a highly coordinated and dynamic interplay between the neutrophil and the endothelial cell that is influenced by the shear forces present at the interface between these two cell types. Chemotactic stimulation of the neutrophil not only induces directed locomotion but markedly alters the surface expression and functions of the neutrophil adhesion molecules, having both an upregulating and downregulating influence. Cytokines such as interleukin 1 induce the synthesis and surface expression of endothelial adhesion molecules such as ICAM-1 and ELAM-1, and stimuli such as thrombin and histamine induce the rapid mobilization to the endothelial surface of another adhesion molecule, GMP-140. Transendothelial migration of neutrophils in most settings both in vitro and in vivo appears to require CD18 integrins on the neutrophil and ICAM-1 on the endothelial cells. This is most clearly demonstrated by the genetic deficiency of CD18 in humans, dogs and cattle, where neutrophil extravasation at most inflammatory sites is almost completely absent. Though the coordinated functions of the various neutrophil and endothelial adhesion molecules are highly efficient in promoting neutrophil extravasation, there has been relatively little investigation of their utilization in tumor cell dissemination. Recent results indicate that such studies may prove fruitful. For example, some adenocarcinoma cell lines express the complex carbohydrate (sialyl Lewis x) recently shown to be a ligand for ELAM-1.

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The importance of neutrophils in resistance to pneumococcal pneumonia in adult and neonatal mice

Garvy

Harmsen

1996

Inflammation

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Neonatal mice succumbed to intranasally-inoculated Streptococcus pneumoniae doses which were as much as 250 times less than the doses that adult mice were resistant to. Neutrophil migration into lungs of neonates was similar in kinetics and intensity to that in adults in response to lethal doses of S. pneumoniae. Interestingly, neutrophil infiltration into the lung alveoli of neonates occurred at lower doses of bacteria than that required for similar responses in adults. Furthermore, depletion of neutrophils in adult and neonatal mice inoculated with low doses of bacteria resulted in significantly higher lung burdens of bacteria in neonatal mice as compared to adults. These data indicate that increased susceptibility of neonates to S. pneumoniae is not the result of incompletely developed neutrophil function and infact, indicate that neutrophils contribute more to resistance to low doses of S. pneumoniae in neonates than they do in adult mice.

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Host Defense Deficiency in Newborn Nonhuman Primate Lungs

Cited by 21 publications

References 17 publications

Abnormalities of LECAM-1- and Mac-1-Dependent Neutrophil-Endothelial Cell Adhesion in the Developing Host

Abnormalities of LECAM-1- and Mac-1-Dependent Neutrophil-Endothelial Cell Adhesion in the Developing Host

PMN adhesion and extravasation as a paradigm for tumor cell dissemination

The importance of neutrophils in resistance to pneumococcal pneumonia in adult and neonatal mice

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