Biology Reference
In-Depth Information
with the anti-polymorphonuclear leukocyte ( PMN ) antibody RB6-8C5. Like-
wise, cytospin examination con®rmed that neutrophils were the most relevant
cell population (55±70% of peritoneal cells), leading to a 70- to 80-fold increase
of the number of cells recovered from the peritoneum with respect to uninjected
mice. In a few days, thymus, spleen and lymph nodes became in®ltrated by
murine granulocytes. Notably, daily treatment of SCID mice with antigranu-
locyte antibody was shown to result in an earlier and more rapid growth of the
human lymphoblastoid and monocytoid cell lines CEM and U937 (Lapenta et
al., 1997), after their subcutaneous injection and an increase of human PBL
persistence in the peritoneal cavity after intraperitoneal inoculation. The gran-
ulocyte reaction of SCID mice is not exclusively directed against human cells
of hematopoietic origin ( Lapenta et al., 1997; Santini et al., 1995). In fact, we
have recently reported that murine granulocytes in®ltrate and delimit human
tumors transplanted in SCID mice and that treatment with antimurine gran-
ulocyte antibody markedly improves the growth of human tumor cell lines of
di¨erent origin, through suppression of the host granulocyte reaction (Lozupone
et al., 2000).
Reverse transcriptuse (RT)-PCR analysis of peritoneal cells reveals that a
wide array of murine cytokines such as interleukin ( IL)-1, IL-4, IL-6, IL-10, IL-
12, tumor necrosis factor ( TNF )-a and interferon ( IFN )-g (with the exception
of IL-2) is rapidly induced after transplantation of human PBL into SCID mice
(Santini et al., 1995). The study of the kinetics of murine cytokine production,
as evaluated by enzyme-linked immunosorkent assay (ELISA) of peritoneal
washings from hu-PBL-SCID mice reveals a peak of TNF-a and IL-12 occur-
ring at 2 h after engraftment, followed by a long lasting induction of IL-6 and
IFN-g, which could be detected in mouse sera for up to 2 wks (Santini et al.,
1995). As a result of human PBL transfer, an impressive increase in murine
leukopoiesis can take place in both bone marrow and spleen, accompanied by
an expansion of the red pulp cells, whereas minimal foci of extramedullary
hematopoiesis are occasionally observed in the liver and peripheral lymph nodes.
FACS analysis of thymocytes from hu-PBL-SCID mice reveals the presence
of CD4
/CD8
/CD3
ÿ
and CD8
/CD3
ÿ
cells between 12 and 14 wks, which
cannot normally be found in unreconstituted mice (Santini et al., 1995).
Human cells residing in hu-PBL-SCID mice are mainly mature CD4 and
CD8 cells. However, CD4 cells in the peritoneal cavity progressively decline
until CD8 cells naturally predominate. Few NK cells and monocytes are re-
covered from mouse peritoneum as soon as 24 h after cell graft and rapidly
become undetectable in peritoneal cell washings, although small adherent foci
of human macrophages can be detected in peritoneal serosa (our unpublished
observations). Even though human B cells rapidly become undetectable in
peritoneal washings, they settle down in mouse organs and undergo a CD4-
dependent conversion into immunoglobulin ( Ig)-producing plasma cells. Thus,
a progressive increase in the detection of human IgG, IgM, and IgA, ranging
from 100 to 500 mg/ml in 2 wks, can be observed in the sera of xenochimeras
( Rizza et al., 1996). Humoral response is preceded by an early and generalized
