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CD99: An endothelial passport for leukocytes.

Hickey MJ - J. Exp. Med. (2015)

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Affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine michael.hickey@monash.edu.

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Complex cellular responses within endothelial cells involving signaling, membrane trafficking, and remodeling of cell–cell junctions are necessary for leukocytes to cross the endothelium and exit the vasculature... In this Issue, Watson et al. describe the signaling pathway activated by CD99 and demonstrate an important role for soluble adenylyl cyclase (sAC) in TEM... Using an elegant imaging-based assay, Watson et al. show that CD99 inhibition prevents movement of the lateral border recycling compartment (LBRC) to the site of TEM, whereas CD99 cross-linking can restore this response, providing evidence of a role for CD99 in signaling for LBRC recycling... Engagement of CD99 leads to activation of sAC and release of cAMP, which subsequently activates PKA, promoting LBRC recycling and facilitating leukocyte TEM... This is the first demonstration of a role for sAC in TEM and of the signaling pathway activated by CD99... The key question to emerge from this study is: can this information be useful therapeutically? However, it remains to be determined how universal this mechanism is within the microvasculature... The current studies were performed using human umbilical vein endothelial cells and mouse dermal microvessels... It is now clear that the mechanisms of leukocyte recruitment can differ markedly in different microvascular beds... Detailed imaging-based analysis of important vascular beds such as the gastrointestinal tract, lung, and brain will be necessary to determine whether CD99 retains this function throughout the microvascular system... In addition, the mechanism whereby PKA promotes LBRC recycling remains to be determined... Unquestionably, the molecular complexity of transmigration will continue to engage the efforts of researchers for many years to come.

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CD99: An endothelial passport for leukocytes.

Hickey MJ - J. Exp. Med. (2015)

Insight from Michael Hickey
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493412&req=5

fig1: Insight from Michael Hickey

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine michael.hickey@monash.edu.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Complex cellular responses within endothelial cells involving signaling, membrane trafficking, and remodeling of cell–cell junctions are necessary for leukocytes to cross the endothelium and exit the vasculature... In this Issue, Watson et al. describe the signaling pathway activated by CD99 and demonstrate an important role for soluble adenylyl cyclase (sAC) in TEM... Using an elegant imaging-based assay, Watson et al. show that CD99 inhibition prevents movement of the lateral border recycling compartment (LBRC) to the site of TEM, whereas CD99 cross-linking can restore this response, providing evidence of a role for CD99 in signaling for LBRC recycling... Engagement of CD99 leads to activation of sAC and release of cAMP, which subsequently activates PKA, promoting LBRC recycling and facilitating leukocyte TEM... This is the first demonstration of a role for sAC in TEM and of the signaling pathway activated by CD99... The key question to emerge from this study is: can this information be useful therapeutically? However, it remains to be determined how universal this mechanism is within the microvasculature... The current studies were performed using human umbilical vein endothelial cells and mouse dermal microvessels... It is now clear that the mechanisms of leukocyte recruitment can differ markedly in different microvascular beds... Detailed imaging-based analysis of important vascular beds such as the gastrointestinal tract, lung, and brain will be necessary to determine whether CD99 retains this function throughout the microvascular system... In addition, the mechanism whereby PKA promotes LBRC recycling remains to be determined... Unquestionably, the molecular complexity of transmigration will continue to engage the efforts of researchers for many years to come.

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