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PMID:23677473

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Citation

Herlihy, SE, Pilling, D, Maharjan, AS and Gomer, RH (2013) Dipeptidyl peptidase IV is a human and murine neutrophil chemorepellent. J. Immunol. 190:6468-77

Abstract

In Dictyostelium discoideum, AprA is a secreted protein that inhibits proliferation and causes chemorepulsion of Dictyostelium cells, yet AprA has little sequence similarity to any human proteins. We found that a predicted structure of AprA has similarity to human dipeptidyl peptidase IV (DPPIV). DPPIV is a serine protease present in extracellular fluids that cleaves peptides with a proline or alanine in the second position. In Insall chambers, DPPIV gradients below, similar to, and above the human serum DPPIV concentration cause movement of human neutrophils away from the higher concentration of DPPIV. A 1% DPPIV concentration difference between the front and back of the cell is sufficient to cause chemorepulsion. Neutrophil speed and viability are unaffected by DPPIV. DPPIV inhibitors block DPPIV-mediated chemorepulsion. In a murine model of acute respiratory distress syndrome, aspirated bleomycin induces a significant increase in the number of neutrophils in the lungs after 3 d. Oropharyngeal aspiration of DPPIV inhibits the bleomycin-induced accumulation of mouse neutrophils. These results indicate that DPPIV functions as a chemorepellent of human and mouse neutrophils, and they suggest new mechanisms to inhibit neutrophil accumulation in acute respiratory distress syndrome.

Links

PubMed PMC3756559 Online version:10.4049/jimmunol.1202583

Keywords

Animals; Chemotaxis, Leukocyte/immunology; Dipeptidyl Peptidase 4/chemistry; Dipeptidyl Peptidase 4/immunology; Dipeptidyl Peptidase 4/metabolism; Disease Models, Animal; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Neutrophil Infiltration/immunology; Neutrophils/immunology; Neutrophils/metabolism; Protein Structure, Quaternary; Respiratory Distress Syndrome, Adult/immunology; Respiratory Distress Syndrome, Adult/pathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:DPP4

GO:0090024: negative regulation of neutrophil chemotaxis

ECO:0000315:

P

Figure(3) shows that human neutrophils in a DPPIV gradient with a DPPIV inhibitor demonstrated significantly less chemorepellent activity than neutrophils in just a DPPIV gradient.

complete
CACAO 13058

HUMAN:DPP4

GO:0045499: chemorepellent activity

ECO:0000314:

F

Figures (2) show that human neutrophils in a DPPIV gradient with a DPPIV inhibitor demonstrated significantly less chemorepellent activity than neutrophils in just a DPPIV gradient.

complete
CACAO 13059

HUMAN:DPP4

GO:0045499: chemorepellent activity

ECO:0000315:

F

Figure (3) shows that human neutrophils in a DPPIV gradient with a DPPIV inhibitor demonstrated significantly less chemorepellent activity than neutrophils in just a DPPIV gradient.

complete
CACAO 13085

Notes

See also

References

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