Lipopolysacchride exposure in newborn rats increases mast cell infiltration in the carotid body and attenuates hypoxic chemosensitivity (873.9)

Abstract

Inflammation adversely modifies carotid body (CB) structure and chemosensitivity in adult animals[1] . Since newborn infants are vulnerable to infections and have unstable breathing, we determined the effect of inflammation on the CB structure and function in newborn rat pups. Pups were given LPS (0.1mg/kg; IP) or saline at postnatal day 2 (P2). Histological sections of the CB were examined for inflammatory cells at P4 (n=7) and P9‐12 (n=6). After LPS exposure, only mast cells were seen, often encircling the CB, and clustered within the CSN as it entered the CB. Mast cells per section (mean±SEM) was higher at P9‐12 in LPS (7.4±1.5) vs saline (5.4±1.4) exposed animals (p=0.04). Surprisingly, more mast cells were seen at 7‐10 days vs 48hrs after LPS exposure. At P21 we also measured carotid sinus nerve (CSN) activity in vitro, in superfused preparations (preps) from LPS (n=8) and saline (n=8) exposed animals. LPS exposure attenuated the peak hypoxic response. In response to hypoxia, CSN (impulses/sec) increased in both groups, but peaked and plateaued at 4 mins vs 6 mins in preps from LPS and saline exposed animals, respectively. Mast cells release pro and anti‐inflammatory cytokines, growth factors, tryptase, and neuromodulators which modify the microenvironment and sensitivity of sensory neurons. Inflammation induces mast cell infiltration in the CB and may attenuate hypoxic chemosensitivity several weeks after the initial inflammatory event during early postnatal development.