Comparison of Gfap Expression and Mucosal Mast Cell Numbers in Pediatric Intestinal Diseases
Eumenia Castro*1, John Ozolek1, Kelly a. Miller2
1Pathology, Children's Hospital of Pittsburgh, Pittsburgh, PA; 2Surgery, Children's Hospital of Pittsburgh, Pittsburgh, PA
Background: Enteric glia likely play major roles in gut barrier function and vascular integrity. Glial fibrillary acidic protein (GFAP) expression is decreased in Crohn’s, Hirschsprung Disease (HD), and necrotizing enterocolitis (NEC). Inflammatory cells including mast cells are present in normal bowel and evidence suggests a functional interaction between mast cells and enteric glia in diseased bowel. The aims are to enumerate and delineate the relationship between enteric glia and mucosal mast cell number in pediatric diseased bowel.Design: Paraffin-embedded colon from 47 cases of ulcerative colitis (UC), resolved NEC (R-NEC), acute NEC (A-NEC), ischemic bowel (ISC), HD associated with inflammation (HDI), HD, and normal (NL) were stained for GFAP and mast cell tryptase. All stain controls were appropriate. Glial cells with a visible process and cytoplasmic staining for GFAP were counted in myenteric (M) and submucosal (S) plexi. In HD, cells were counted in ganglionic (G), transitional zone (TZ), and aganglionic segments (AG). Non-parametric analysis was done with p-values <0.05 significant. Results are shown as density (median number of cells per centimeter; minimum and maximum values in parentheses).
Results: Glial cells (M) were greater than glial cells (S) except in UC where UC demonstrated the highest median number of glial (S). Glial (M) in ISC and A-NEC were significantly higher than glial (S). While glial cells within the ganglionic segment of HDI were greater than in the TZ, this was not statistically significant. UC and NL had significantly higher number of mast cells compared to other groups (p<0.05). The number of mast cells did not differ between the G, TZ, and AG segments in either HDI or HD. A-NEC had the highest ratio of glial (M) to mast cell number (1.18) while A-NEC, HDI, and HD had the highest ratio of glial (S) to mast cell number (0.10, 0.17, and 0.095 respectively).
Conclusion: Mast cell numbers appear increased in UC. HD shows decreased myenteric glial cells compared to other groups except NL. Other conditions including HD show decreased numbers of mast cells compared to NL and UC. We speculate that mucosal mast cells may exert an effect on expression of GFAP within submucosal glial cells under chronic inflammatory conditions.
N | GFAP#-G-M | GFAP#-G-S | GFAP#-TZ-M | GFAP#-TZ-S | MAST CELL#-G | MAST CELL#-AG | MAST CELL#-TZ | |
NL | 8 | 0 (0,53) | 0 (0,2) | - | - | 110 (45,72) | - | - |
UC | 7 | 12 (0,30) | 12 (0,50) | - | - | 180 (57,222) | - | - |
HDI | 7 | 30 (2,55) | 10 (0,41) | 7.5 (0,49) | 9 (0,35) | 51 (39,110) | 40 (22,45) | 51.5 (20,68) |
HD | 6 | 3.5 (0,49) | 3 (0,8) | 5 (0,23) | 6 (1,15) | 43 (18,66) | 44.5 (21,63) | 40 (26,56) |
ISC | 7 | 36 (0,72) | 0 (0,3) | - | - | 64 (28,180) | - | - |
A-NEC | 7 | 30 (0,80) | 1 (0,15) | - | - | 29 (9,72) | - | - |
R-NEC | 5 | 22 (0,75) | 0 (0,10) | - | - | 62 (46,90) | - | - |