Regular ArticleNeutrophil CD40 enhances platelet-mediated inflammation
Section snippets
Chemicals and reagents
Prostaglandin E1 (PGE1), lucigenin, sodium citrate, NaH2PO4 and dextrose, fMLP (N-formyl-Met-Leu-Phe), N-acetylcysteine, wortmannin, and α-Lipoic acid were purchased from Sigma-Aldrich (St. Louis, MO). LY294002 was purchased from Cayman Chemicals (Ann Arbor, MI). Fibrinogen and human alpha thrombin were purchased from Enzyme Research Laboratories (South Bend, IN). Thrombin Receptor Activation Peptide (TRAP1–6) was purchased from Peninsula Laboratories (San Carlos, CA).
Statistics
All data are presented as mean ± standard error. Significance of difference between groups was evaluated with one-way analysis of variance (ANOVA). Statistical significance was accepted with a P value < 0.05.
CD40 is present in neutrophils
Initially, to identify CD40, neutrophil mRNA was isolated from six different donors. Real-time PCR was used to quantify the CD40 mRNA transcripts after normalization with β-actin (Fig. 1a, left panel). These data confirm the presence of CD40 in neutrophils consistent with the recent report by Khan et al. [6]. Notably, the relative abundance of CD40 in neutrophils is less than that in platelets and almost a hundred-fold less than that in the proplatelet cell line MEG01 (Fig. 1a, left panel). The
Discussion
Platelets play a significant role in the development of thrombosis and inflammation. Platelets interact with monocytes via a CD40–CD40L-mediated pathway that causes their adherence to the inflamed endothelial layer [32], [33], [34]. Neutrophils are also known to be central to many inflammatory processes and were recently reported to express CD40 [6]. Khan and colleagues [6] showed that sCD40L, which accumulates during blood component storage, has the capacity to activate adherent neutrophils
Acknowledgements
We gratefully acknowledge the help of Dr. Kahraman Tanriverdi and Kristine Morin for real-time PCR analysis. We are also thankful to Dr. Michael Kirber for his help during two-photon confocal microscopic studies.
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