Calcitonin gene related peptide and N-procalcitonin modulate CD11b upregulation in lipopolysaccharide activated monocytes and neutrophils.
OBJECTIVE
Circulating levels of calcitonin gene related peptide (CGRP) and calcitonin precursors, including procalcitonin (PCT) and its free aminopeptide N-procalcitonin (N-PCT), have been found dramatically increased in septic patients. PCT is known to attenuate the chemotaxis of monocytes in response to chemoattractants. This study examined whether CGRP and N-PCT modulate the LPS-induced expression of CD11b, which is one of the major integrins involved in monocyte and neutrophil chemotaxis during a response to microbial infections.


METHODS
In vitro cell culture study in the immunology laboratory of a university hospital.


METHODS
Healthy volunteers.


RESULTS
We assessed the effects of N-PCT and CGRP on CD11b expression on monocytes and neutrophils after LPS (2 ng/ml) or fMLP (10(-8) M) challenges. We used a human whole blood model, and measurements were made by flow cytometry. Both peptides in a dose-dependent manner decreased the LPS- and fMLP-induced rise in CD11b in monocytes and neutrophils. As these peptides are thought to act by raising cAMP, we also mimicked their effects with the use of rolipram and forskolin and found similar results.


CONCLUSIONS
These findings are in line with recent studies demonstrating anti-inflammatory properties for this family of peptides. CGRP and calcitonin precursors may function as factors suppressing the propagation of inflammation through the inhibition of several processes involved during a response to a bacterial stimulus.
Monneret
Guillaume
G
Immunology Laboratory and Intensive Care Unit, Lyon-Sud University Hospital, 69495, Pierre-Bénite, France. guillaume.monneret@chu-lyon.fr.
Arpin
Maud
M
Immunology Laboratory and Intensive Care Unit, Lyon-Sud University Hospital, 69495, Pierre-Bénite, France.
Venet
Fabienne
F
Immunology Laboratory and Intensive Care Unit, Lyon-Sud University Hospital, 69495, Pierre-Bénite, France.
Maghni
Karim
K
Research Centre, Unit of Respiratory Diseases, Sacré-Coeur Hospital, Université de Montréal, Montreal, Canada.
Debard
Anne-Lise
AL
Immunology Laboratory and Intensive Care Unit, Lyon-Sud University Hospital, 69495, Pierre-Bénite, France.
Pachot
Alexandre
A
Immunology Laboratory and Intensive Care Unit, Lyon-Sud University Hospital, 69495, Pierre-Bénite, France.
Lepape
Alain
A
Immunology Laboratory and Intensive Care Unit, Lyon-Sud University Hospital, 69495, Pierre-Bénite, France.
Bienvenu
Jacques
J
Immunology Laboratory and Intensive Care Unit, Lyon-Sud University Hospital, 69495, Pierre-Bénite, France.
D015415:Biomarkers / Q000097:blood; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D002116:Calcitonin / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D008070:Lipopolysaccharides / Q000009:adverse effects; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011498:Protein Precursors / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology*
D015415:Biomarkers; C000606589:CALCA protein, human; D039481:CD11b Antigen; D008070:Lipopolysaccharides; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002116:Calcitonin; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D020889:Rolipram