Abstract
Introduction: Hemolymph nodes, characterized by erythrocyte rosettes, are found in humans and animals, including rats. The cytoarchitectural features that these nodes exhibit compared with those of ordinary lymph nodes and spleen are unknown. Herein, we describe the cytoarchitecture of rat hemolymph nodes. Methods: We performed immunohistochemical analyses with antibodies against CD68, Iba-1, CD3, CD20, and S-100. Hematoxylin and eosin staining was used to compare findings with sections from ordinary lymph nodes and spleen. Results: Hemolymph nodes exhibited erythrocyte rosettes with macrophages immunopositive for CD68, Iba-1, and CD3, which were rare in the physiologically normal spleen and lymph nodes. Additionally, sinusoidal macrophages often showed close apposition to erythrocytes and mast cells. Accumulation of cells immunoreactive to CD20, a B-lymphocyte marker, was seen only in the germinal centers of ordinary lymph nodes, not in the hemolymph nodes or spleen. Ordinary lymph nodes and spleen showed well-developed reticular configurations of cells with immunoreactivity for S-100, a marker for dendritic cells, unlike hemolymph nodes, suggesting less-developed antigen-presenting ability in the latter. Despite similarities to ordinary lymph nodes and spleen, the direct contact with erythrocytes and mast cells in the hemolymph nodes suggests a facilitation of direct cell-to-cell communication for macrophages, erythrocytes, and mast cells. Conclusion: Our findings imply that the hemolymph nodes are a unique immune organ, differing from ordinary lymph nodes and spleen.
Journal Section:
Developmental Biology
References
1.
Dohi
A
, Noguchi
T
, Yamashita
M
, Sasaguri
K
, Yamamoto
T
, Mori
Y
. Acute stress transiently activates macrophages and chemokines in cervical lymph nodes
. Immunol Res
. 2024
;72
(2
):212
–24
. 2.
Gibbes
H
. Memoirs: on some structures found in the connective tissue between the renal artery and vein in the human subject
. J Cell Sci
. 1884
;2
:186
–90
.3.
Robertson
WF
. The prevertebral hæmolymph glands
. Lancet
. 1890
;136
(3509
):1152
–4
. 4.
Warthin
AS
. The normal histology of the human hemolymph glands
. Am J Anat
. 1901
;1
(1
):63
–79
. 5.
Abu-Hijleh
MF
, Scothorne
RJ
. Studies on haemolymph nodes. IV. Comparison of the route of entry of carbon particles into parathymic nodes after intravenous and intraperitoneal injection
. J Anat
. 1996
;188
(Pt 3
):565
–73
.6.
Sakita
K
, Fujino
M
, Koshikawa
T
, Ohmiya
N
, Ohbayashi
M
, Asai
J
. Structure and function of the hemolymph node in rats
. Nagoya J Med Sci
. 1997
;60
(3–4
):129
–37
.7.
Gargiulo
AM
, Ceccarelli
P
, Pedini
V
. Architecture of sheep haemal nodes
. Res Vet Sci
. 1987
;42
(3
):280
–6
. 8.
Ezeasor
DN
, Singh
A
. Histology of the caprine hemal node
. Acta Anat
. 1988
;133
(1
):16
–23
. 9.
Galeotti
M
, Sarli
G
, Eleni
C
, Marcato
PS
. Identification of cell types present in bovine haemolymph nodes and lymph nodes by immunostaining
. Vet Immunol Immunopathol
. 1993
;36
(4
):319
–31
. 10.
Cerutti
P
, Guerrero
F
. Identification of positive cells to interleukin-4 in bovine haemal nodes
. Anat Histol Embryol
. 2001
;30
(4
):219
–23
. 11.
Zidan
M
, Pabst
R
. Histological, histochemical and immunohistochemical study of the haemal nodes of the dromedary camel
. Anat Histol Embryol
. 2004
;33
(5
):284
–9
. 12.
Yamamoto
T
, Yamashita
A
, Yamada
K
, Hata
R-I
. Immunohistochemical localization of chemokine CXCL14 in rat hypothalamic neurons
. Neurosci Lett
. 2011
;487
(3
):335
–40
. 13.
Turner
DR
. The vascular tree of the haemal node in the rat
. J Anat
. 1969
;104
(Pt 3
):481
–93
.14.
Kazeem
AA
, Reid
O
, Scothorne
RJ
. Studies on hemolymph nodes. I. Histology of the renal hemolymph node of the rat
. J Anat
. 1982
;134
(Pt 4
):677
–83
.15.
Van den Broeck
W
, Derore
A
, Simoens
P
. Anatomy and nomenclature of murine lymph nodes: descriptive study and nomenclatory standardization in BALB/cAnNCrl mice
. J Immunol Methods
. 2006
;312
(1–2
):12
–9
. 16.
Pan
W-R
, Liu
Z
, Sun
D-X
, Song
L
, Ma
C-X
, Dong
H-Y
, et al. Hemolymph node: an immunomorphlogical organ – modeling the hemolymph node by allografting renal tissue in the rat
. Cells Tissues Organs
. 2023
;212
(2
):147
–54
. 17.
Nopajaroonsri
C
, Luk
SC
, Simon
GT
. The structure of the hemolymph node: a light, transmission, and scanning electron microscopic study
. J Ultastruct Res
. 1974
;48
(3
):325
–41
. 18.
Ohsawa
K
, Imai
Y
, Kanazawa
H
, Sasaki
Y
, Kohsaka
S
. Involvement of Iba1 in membrane ruffling and phagocytosis of macrophages/microglia
. J Cell Sci
. 2000
;113
(Pt 17
):3073
–84
. 19.
Yang
ZF
, Ho
DW
, Lau
CK
, Lam
CT
, Lum
CT
, Poon
RTP
, et al. Allograft inflammatory factor-1 (AIF-1) is crucial for the survival and pro-inflammatory activity of macrophages
. Int Immunol
. 2005
;17
(11
):1391
–7
. 20.
Tian
Y
, Kelemen
SE
, Autieri
MV
. Inhibition of AIF-1 expression by constitutive siRNA expression reduces macrophage migration, proliferation, and signal transduction initiated by atherogenic stimuli
. Am J Physiol Cell Physiol
. 2006
;290
(4
):C1083
–91
. 21.
Imai
Y
, Ibata
I
, Ito
D
, Ohsawa
K
, Kohsaka
S
. A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage
. Biochem Biophys Res Commun
. 1996
;224
(3
):855
–62
. 22.
Wijesundera
KK
, Juniantito
V
, Golbar
HM
, Fujisawa
K
, Tanaka
M
, Ichikawa
C
, et al. Expressions of Iba1 and galectin-3 (Gal-3) in thioacetamide (TAA)-induced acute rat liver lesions
. Exp Toxicol Pathol
. 2013
;65
(6
):799
–808
. 23.
Cora
MC
, Janardhan
KS
, Jensen
H
, Clayton
N
, Travlos
GS
. Previously diagnosed reticulum cell hyperplasia in decalcified rat bone marrow stain positive for ionized calcium binding adapter molecule 1 (Iba1): a monocytic/macrophage cell marker
. Toxicol Pathol
. 2020
;48
(2
):317
–22
. 24.
Kojo
A
, Yamada
K
, Kubo
K-Y
, Yamashita
A
, Yamamoto
T
. Occlusal disharmony in mice transiently activates microglia in hippocampal CA1 region but not in dentate gyrus
. Tohoku J Exp Med
. 2010
;221
(3
):237
–43
. 25.
Yamashita
A
, Kunimatsu
T
, Yamada
K
, Kojo
A
, Yamamoto
T
, Sato
S
, et al. Hypothermic and normothermic ischemia-reperfusion activate microglia differently in hippocampal formation
. Arch Histol Cytol
. 2010
;73
(2
):73
–80
. 26.
Wijesundera
KK
, Izawa
T
, Tennakoon
AH
, Murakami
H
, Golbar
HM
, Katou-Ichikawa
C
, et al. M1- and M2-macrophage polarization in rat liver cirrhosis induced by thioacetamide (TAA), focusing on Iba1 and galectin-3
. Exp Mol Pathol
. 2014
;96
(3
):382
–92
. 27.
Galli
SJ
, Grimbaldeston
M
, Tsai
M
. Immunomodulatory mast cells: negative, as well as positive, regulators of immunity
. Nat Rev Immunol
. 2008
;8
(6
):478
–86
. 28.
Abraham
SN
, St John
AL
. Mast cell-orchestrated immunity to pathogens
. Nat Rev Immunol
. 2010
;10
(6
):440
–52
. 29.
Simson
JV
, Spicer
SS
. Ferritin particles in macrophages and in associated mast cells
. J Cell Biol
. 1972
;52
(3
):536
–41
. 30.
Klopfleisch
R
. Macrophage reaction against biomaterials in the mouse model: phenotypes, functions and markers
. Acta Biomater
. 2016
;43
:3
–13
. 31.
Shapouri-Moghaddam
A
, Mohammadian
S
, Vazini
H
, Taghadosi
M
, Esmaeili
S-A
, Mardani
F
, et al. Macrophage plasticity, polarization, and function in health and disease
. J Cell Physiol
. 2018
;233
(9
):6425
–40
. 32.
Bozkurt
YA
, Kabak
M
, Başak
F
, Onuk
B
. The localization of CD3, CD79a, CD68 and S100 protein immunoreactive cells in hemal nodes of Saanen goat (Capra hircus)
. Biotech Histochem
. 2018
;93
(7
):536
–40
. 33.
Beham
AW
, Puellmann
K
, Laird
R
, Fuchs
T
, Streich
R
, Breysach
C
, et al. A TNF-regulated recombinatorial macrophage immune receptor implicated in granuloma formation in tuberculosis
. PLoS Pathog
. 2011
;7
(11
):e1002375
. 34.
Chavez-Galan
L
, Vesin
D
, Blaser
G
, Uysal
H
, Benmerzoug
S
, Rose
S
, et al. Myeloid cell TNFR1 signaling dependent liver injury and inflammation upon BCG infection
. Sci Rep
. 2019
;9
(1
):5297
. 35.
Rodriguez-Cruz
A
, Vesin
D
, Ramon-Luing
L
, Zuñiga
J
, Quesniaux
VFJ
, Ryffel
B
, et al. CD3+ macrophages deliver proinflammatory cytokines by a CD3- and transmembrane TNF-dependent pathway and are increased at the BCG-infection site
. Front Immunol
. 2019
;10
:2550
. 36.
Lanier
LL
, Chang
C
, Spits
H
, Phillips
JH
. Expression of cytoplasmic CD3 epsilon proteins in activated human adult natural killer (NK) cells and CD3 gamma, delta, epsilon complexes in fetal NK cells. Implications for the relationship of NK and T lymphocytes
. J Immunol
. 1992
;149
(6
):1876
–80
. 37.
Takahashi
K
, Isobe
T
, Ohtsuki
Y
, Sonobe
H
, Takeda
I
, Akagi
T
. Immunohistochemical localization and distribution of S-100 proteins in the human lymphoreticular system
. Am J Pathol
. 1984
;116
(3
):497
–503
.38.
Atoji
Y
, Suzuki
Y
. Immunohistochemical study of S-100 protein in the bovine lymph node and spleen
. Okajimas Folia Anat Jpn
. 1990
;67
(4
):257
–61
. 39.
Knight
SC
, Stagg
AJ
. Antigen-presenting cell types
. Curr Opin Immunol
. 1993
;5
(3
):374
–82
. 40.
Reis e Sousa
C
. Activation of dendritic cells: translating innate into adaptive immunity
. Curr Opin Immunol
. 2004
;16
(1
):21
–5
. © 2025 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2025
You do not currently have access to this content.
