Inflammatory mediators and cellular infiltration of the lungs in a guinea pig model of the late asthmatic reaction.
Alterations in cell numbers, vascular permeability, and concentrations of various inflammatory mediators in the lung were measured in a guinea pig model of the late asthmatic reaction. Animals sensitized by inhalation of ovalbumin were challenged with an aerosol of ovalbumin or saline, and bronchoalveolar lavage fluid (BALF) and peripheral blood were collected after periods ranging from 5 min to 72 h. Increased vascular leakage within the lungs was indicated by elevated BALF/plasma albumin ratios at all time points, and was maximal 6 h after challenge. There were increased numbers of eosinophils in BALF by 6 h after challenge and they remained elevated at least until 72 h. A corresponding increase in the proportion of blood leukocytes represented by eosinophils was observed at 6 and 17 h, which suggests that these cells may be drawn to the lung following their release into the circulation, but by 72 h the proportion in blood had returned to normal. A transitory neutrophilia was evident in BALF and blood 6 h after allergen exposure, but there were no allergen-induced changes in BALF numbers of macrophages, lymphocytes, epithelial cells, or mast cells (as assessed by concentrations of cell-associated histamine). beta-Glucuronidase activity was significantly increased in BALF of guinea pigs at 2 h and 17 h following challenge. The degree to which eicosanoids can be recovered in BALF was investigated by instilling a range of tritiated compounds into the lungs of normal guinea pigs at the time of lavage. Ratio high-performance liquid chromatography revealed that there had been little metabolism of the eicosanoids recovered in BALF. However, there was evidence for a rapid removal of these mediators from the lung, a process which will militate against their accurate quantitation in BALF. Histamine, prostaglandin D2, and thromboxane B2 were detected in BALF but did not differ between treatment groups, and levels showed no simple relationship with the other inflammatory changes measured.
Walls
A F
AF
Immunopharmacology Group, University of Southampton, Southampton General Hospital, UK.
Rhee
Y K
YK
Gould
D J
DJ
Walters
C
C
Robinson
C
C
Church
M K
MK
Holgate
S T
ST
D000418:Albumins / Q000032:analysis; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D005966:Glucuronidase / Q000032:analysis; D006168:Guinea Pigs; D006632:Histamine / Q000032:analysis; D007249:Inflammation; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D015230:Prostaglandin D2 / Q000032:analysis; D013929:Thromboxane B2 / Q000032:analysis
D000418:Albumins; D013929:Thromboxane B2; D006632:Histamine; D010047:Ovalbumin; D005966:Glucuronidase; D015230:Prostaglandin D2