Does Migration Pathway Influence the Fate of the Neutrophil?

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William Elaban Chanchal Sur Chowdhury


By William Elaban, Biological Sciences

Advisor: Chanchal Sur Chowdhury

Presentation ID: AM_D12

Abstract: Neutrophils are known as principal responders to tissue injury or infection. Upon initiation of inflammation, they migrate rapidly through the postcapillary venule wall into peripheral tissue, in a sequence of adhesion and activation events, known as the neutrophil extravasation cascade. A critical step in that process is neutrophil migration across the endothelium, or �diapedesis.��Interestingly, diapedesis can occur between or through endothelial cells (paracellular or transcellular, respectively).�Although neutrophil extravasation is an integral part host defense mechanism, aberrant neutrophil infiltration into tissue is associated with tissue damage and numerous pathogenic conditions such as ischemia-reperfusion (I-R) injury, rheumatoid arthritis, and atherosclerosis. Despite the clinical importance, the mechanisms of neutrophil migration into tissues, notably diapedesis and its consequences, remain poorly understood. The small GTPase, Rap1b controls multiple cellular processes including cell adhesion, growth and differentiation, in various cell types. However, we found that Rap1b-deficient mice exhibited enhanced neutrophil recruitment to inflamed lungs and susceptibility to endotoxin shock. The increased diapedesis was found to be associated with selective increase in trans-cellular mode of migration, over the classical para-cellular. Following diapedesis neutrophil respond to infection or inflammation by its effector functions such as degranulation, phagocytosis, reactive oxygen species generation and neutrophil extracellular traps formation.�Here, we used Rap1b-/-�mice as a model of upregulated transcellular migration, to examine whether transcellular migration primes neutrophils towards a specific function.�Using immunofluorescent microscopy, ELISA and proteomics of neutrophils migrated into LPS mediated lung infection model, we will examine�how distinct migration paths impact outcome of inflammation.

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AM Poster Session -- Great Hall -- D: New Frontiers