title: Quantifying the Sensitivity of Human Immune Cells to Chemoattractant.
abstract: The efficient recruitment of immune cells is a vital cornerstone of our defense against infections and a key challenge of immunotherapeutic applications. It relies on the ability of chemotaxing cells to prioritize their responses to different stimuli. For example, immune cells are known to abandon gradients of host-cell-produced cytokines in favor of complement-derived anaphylatoxins, which then guide the cells toward nearby pathogen surfaces. The aptitude to triage stimuli depends on the cells' specific sensitivities to different chemoattractants. We here use human neutrophils as uniquely capable biodetectors to map out the anaphylatoxic cloud that surrounds microbes in the presence of host serum. We quantify the neutrophil sensitivity in terms of the ratio between the chemoattractant concentration c and the production rate j0of the chemoattractant at the source surface. An integrative experimental/theoretical approach allows us to estimate the c/j0-threshold at which human neutrophils first detect nearby β-glucan surfaces as c/j0≈ 0.0044 s/μm.
authors.affiliation: Department of Biomedical Engineering, University of California at Davis, Davis, California.
authors.forename: Emmet A
authors.initials: EA
authors.lastname: Francis
authors.affiliation: Department of Biomedical Engineering, University of California at Davis, Davis, California. Electronic address: volkmar@gmail.com.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Heinrich
mesh_terms: D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D015936:Complement C5a / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology
chemical_list: D002630:Chemotactic Factors; D047071:beta-Glucans; D015936:Complement C5a