Browsing by Author "Podstawka, John"

Now showing 1 - 1 of 1
  • Thumbnail Image
    ItemOpen Access
    Investigating pulmonary vascular B cells
    (2019-04-26) Podstawka, John; Yipp, Bryan G.; Hirota, Simon Andrew; Kelly, Margaret Mary; Flannigan, Kyle L.
    The lung is a vital organ which is required for gas exchange. The anatomy of the lung itself, immune molecules, and leukocytes provide the host with protection from harmful debris and pathogenic stimuli. A component of pulmonary host defense is neutrophils which are found within the lung capillary network. Within the pulmonary capillaries, there is a population of neutrophils which remains adherent to the vascular endothelium for extended periods of time and exhibits marginated behaviour. While pulmonary vascular neutrophils are important in the acute immune response of the lung, they tend to exhibit an aged and pro-inflammatory phenotype. While inflammation within the lung is necessary for host defence and is a part of wound healing, cellular infiltration of the lung significantly compromises oxygen delivery and carbon dioxide removal. Therefore, pulmonary inflammation must be tightly controlled and regulated. We previously determined that pulmonary vascular B cells regulate neutrophils via CD18-mediated interactions, labelling them MHCII+AnnexinV+, and that in the absence of B cells, the lung will develop pathological fibrotic interstitial lung disease. In this body of work, we determined that pulmonary intravascular B cells can marginate which allows them to specialize in regulating lung neutrophils. These B cells exhibit a mature, naïve, conventional B2 cell phenotype, and engage in marginated behaviour which can be mediated by CD49e or via CXCR5/CXCL13. Blocking CD49e decreased the amount B cell-neutrophil interactions taking place within the lung capillaries, and providing exogenous CXCL13 or neutralizing endogenous CXCL13 would respectively increase and decrease the amount of interactions. Moreover, we demonstrated an intratracheal injection of CXCL13 increased the number of neutrophils which exhibited an MHCII+AnnexinV+ phenotype; indicating increased regulation via B cell interactions. Thus, we acquired novel insight into how lung intravascular B cells are engaging in prolonged interactions with lung neutrophils; interactions which were previously defined as regulatory and important for maintaining inflammatory homeostasis.