By Frank Entschladen, Kurt S. Zanker

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Additional resources for Cell Migration: Signalling and Mechanisms (Translational Research in Biomedicine, Vol. 2)

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The circulating cell is globular, which is the optimum geometrical form for minimizing drag. When the circulating leukocyte senses a chemoattractant gradient, it rolls over the endothelium thanks to the interaction of selectin proteins with their ligand, and comes to a stop over the endothelium through the generation of firm adhesions through integrins. To prevent dispersion of the chemoattractant, chemokines are held on the endothelial cell surface by extracellular matrix molecules and proteoglycans.

Patients with WHIM syndrome (warts, hypogammaglobulinemia, recurrent bacteria infections, and myelokathexis) have neutrophil retention in the bone marrow and neutropenia resulting in recurrent bacterial infections. Patients with the dominantly-inherited WHIM syndrome have mutations in CXCR4, a receptor that recognizes CXCL12 (SDF-1) [39]. WHIM syndrome-associated mutations have a truncation of the cytoplasmic carboxyl-(C)-terminal tail of the receptor preventing downregulation of the receptor [40].

Many autoinflammatory diseases are hereditary and monogenetic including familial Mediterranean fever (FMF) and the cryopyrin-associated periodic syndromes (CAPS) including neonatal-onset multisystem inflammatory disease (NOMID), Muckle-Wells syndrome (MWS), and familial cold autoinflammatory syndrome (FCAS). Pyogenic sterile arthritis with pyoderma gangrenosum and acne (PAPA) syndrome and tumor necrosis factor receptor (TNFR)-associated periodic syndrome (TRAPS) are also inherited autoinflammatory diseases.

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